Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem.

The clinical profile of SC is considerably broader than reported previously. Cardiovascular magnetic resonance imaging at the time of initial clinical presentation may provide relevant functional and tissue information that might aid in the establishment of the diagnosis of SC.

Diazotrophic marine cyanobacteria in the genus Trichodesmium contribute a large fraction of the new nitrogen entering the oligotrophic oceans, but little is known about how they respond to shifts in global change variables such as carbon dioxide (CO 2 ) and temperature. We compared Trichodesmium dinitrogen (N 2 ) and CO 2 fixation rates during steady-state growth under past, current, and future CO 2 scenarios, and at two relevant temperatures. At projected CO 2 levels of year 2100 (76 Pa, 750 ppm), N 2 fixation rates of Pacific and Atlantic isolates increased 35-100%, and CO 2 fixation rates increased 15-128% relative to present day CO 2 conditions (39 Pa, 380 ppm). CO 2 -mediated rate increases were of similar relative magnitude in both phosphorus (P)-replete and P-limited cultures, suggesting that this effect may be independent of resource limitation. Neither isolate could grow at 15 Pa (150 ppm) CO 2 , but N 2 and CO 2 fixation rates, growth rates, and nitrogen : phosophorus (N : P) ratios all increased significantly between 39 Pa and 152 Pa (1500 ppm). In contrast, these parameters were affected only minimally or not at all by a 4uC temperature change. Photosynthesis versus irradiance parameters, however, responded to both CO 2 and temperature but in different ways for each isolate. These results suggest that by the end of this century, elevated CO 2 could substantially increase global Trichodesmium N 2 and CO 2 fixation, fundamentally altering the current marine N and C cycles and potentially driving some oceanic regimes towards P limitation. CO 2 limitation of Trichodesmium diazotrophy during past glacial periods could also have contributed to setting minimum atmospheric CO 2 levels through downregulation of the biological pump. The relationship between marine N 2 fixation and atmospheric CO 2 concentration appears to be more complex than previously realized and needs to be considered in the context of the rapidly changing oligotrophic oceans.

Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. In a multicenter noninferiority trial, we randomized 2037 kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m at post-transplant month 12 using a 10% noninferiority margin. In the intent-to-treat population (everolimus =1022, MPA=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events. In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

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